Ectopic expression of Bcl-2, but not Bcl-xL rescues Ramos B cells from Fas-mediated apoptosis.
The human Burkitt lymphoma Ramos B cell line can be induced to undergo apoptosis in response to a variety of different agents, including calcium ionophores, anti-immunoglobulin (Ig) and macromolecular synthesis inhibitors. In addition, following up-regulation of the Fas (CD95) surface receptor by CD40 ligation, these cells also become susceptible to apoptosis induction by Fas ligation. We have previously shown that protection from calcium ionophore- and macromolecular synthesis inhibitor-induced apoptosis by CD40 ligation is associated with a rapid up-regulation of Bcl-xL followed by a more moderate and delayed up-regulation of Bcl-2. We show here that overexpression of Bcl-xL, like Bcl-2, protects Ramos cells from apoptosis induction in response to calcium ionophore, anti-Ig and macromolecular synthesis inhibition. However, in contrast to Bcl-2, ectopic overexpression of Bcl-xL does not rescue from Fas-mediated apoptosis. Thus, in Ramos B cells, the Fas apoptotic pathway exhibits differential sensitivity to inhibition by Bcl-2 family members. These findings also suggest that CD40 signaling provides a switch which renders the cells susceptible to Fas-ligand mediated apoptosis through up-regulation of Fas whilst affording protection from anti-Ig-induced apoptosis through up-regulation of Bcl-xL.
Alam
M K
MK
Infection and Immunity Research Group, Division of Life Sciences, King's College London, GB.
Davison
S
S
Siddiqui
N
N
Norton
J D
JD
Murphy
J J
JJ
D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002051:Burkitt Lymphoma / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein; D019014:fas Receptor / Q000276:immunology*
C494811:BCL2L1 protein, human; D019013:CD40 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor